PhD Position Study Genetic Impacts on Brain Cells Using Single-Cell and Spatial ML Techniques

Join us to decode how genetic variation reprograms brain cells and disrupts their communication using AI 

Job description

We are looking for a PhD student to work at the intersection of machine learning, single-cell genomics, and neurogenetics. Your project will focus on developing new methods to understand how genetic variants affect not only individual brain cells but also change the way cells interact and communicate — insights that are essential for understanding the cellular origins of brain disorders.

Despite major progress in genetics research, we still don’t know how genetic risk factors for brain disorders like schizophrenia, alzheimer, and depression disrupt brain function. Genetic discoveries point to thousands of disease-associated SNPs, but most of them act in subtle and cell type–specific ways, and their downstream biological effects remain poorly understood.

This project tackles this fundamental gap — by building computational models that simulate what goes wrong in the brain, one cell (and one cell–cell interaction) at a time.

You will work with large-scale single-cell and spatial transcriptomics data to develop and apply single-cell foundation models — generative machine learning models that represent the structure and variation of cell states. These models act as virtual cells simulating how perturbing the expression of genes altered by genetic variants affects the cell’s identity, behavior, and trajectory. You will extend these models to understand how genetic risk factors alter cell–cell communication networks. Spatial transcriptomics datasets will be used to anchor these models in real tissue context, revealing how spatially organized cell communities rewire under genetic perturbation.

Key challenges

• Use and improve single-cell foundation models to predict SNP-driven shifts in cell state and cell fate.
• Integrate spatial transcriptomics data to anchor these predictions in tissue context.
• Develop machine learning methods (e.g. graph neural networks, variational or diffusion models) to model cell–cell communication dynamics under genetic perturbation.
• Investigate how local interactions between perturbed and unperturbed cells reshape signaling networks and tissue states.
• Closely collobarate with neuroscientists in the BRAINSCAPES consortium to link model predictions to experimental and clinical relevance.

Benefits

• Shape next-generation models for understanding brain disease mechanisms.
• Work in a collaborative, interdisciplinary, and dynamic environment with leading experts in machine learning, computational biology, and neurogenomics.
• Access cutting-edge datasets, infrastructure, and computational and experimental facilities.
• Receive support for professional development and participation in international conferences.

Job requirements 

• A Master’s degree in computational biology, machine learning, bioinformatics, AI, or a related field.
• Strong background in machine learning and data analysis.
• Interest in single-cell omics, spatial data, or systems neuroscience.
• Intellectual curiosity, independence, and motivation to tackle open-ended problems with real-world impact.
• Strong analytical thinking and problem-solving skills.
• A passion for using AI to answer fundamental questions in biology and medicine.
• Ability to work independently and as part of a multidisciplinary team.
• Strong interpersonal communication and collaboration abilities
• Strong communication skills and proficiency in English.

Conditions of employment 

Doctoral candidates will be offered a 4-year period of employment in principle, but in the form of 2 employment contracts. An initial 1,5 year contract with an official go/no go progress assessment within 15 months. Followed by an additional contract for the remaining 2,5 years assuming everything goes well and performance requirements are met. 

Salary and benefits are in accordance with the Collective Labour Agreement for Dutch Universities , increasing from €3059 - €3881 gross per month, from the first year to the fourth year based on a fulltime contract (38 hours), plus 8% holiday allowance and an end-of-year bonus of 8.3%.  

As a PhD candidate you will be enrolled in the TU Delft Graduate School. The TU Delft Graduate School provides an inspiring research environment with an excellent team of supervisors, academic staff and a mentor. The Doctoral Education Programme is aimed at developing your transferable, discipline-related and research skills. 

The TU Delft offers a customisable compensation package, discounts on health insurance, and a monthly work costs contribution. Flexible work schedules can be arranged.  

Will you need to relocate to the Netherlands for this job? TU Delft is committed to make your move as smooth as possible! The HR unit, Coming to Delft Service, offers information on their website to help you prepare your relocation. In addition, Coming to Delft Service organises events to help you settle in the Netherlands, and expand your (social) network in Delft. A Dual Career Programme is available, to support your accompanying partner with their job search in the Netherlands.  

Additional information

This PhD position is positioned within the Delft Bioinformatics Lab, part of the Computer Science department of the Delft University of Technology under supervision of Prof. Marcel Reinders, m.j.t.reinders@tudelft.nl, and Ahmed Mahfouz from the Leiden University Medical Center, a.mahfouz@lumc.nl, in close collaboration with BRAINSCAPES scientists across the Netherlands.

Application procedure

Are you interested in this vacancy? Please apply no later than 16 November 2025 via the application button and upload the following documents:

• An up-to-date and detailed curriculum vitae.
• Copies of relevant academic transcripts.
• A cover letter, which should summarize (1) why the applicant wants the position, (2) why the project is of interest to the applicant, (3) evidence of suitability for the job, and (4) what the applicant hopes to gain from the position.

You can address your application to Marcel Reinders and Ahmed Mahfouz.

Doing a PhD at TU Delft requires English proficiency at a certain level to ensure that the candidate is able to communicate and interact well, participate in English-taught Doctoral Education courses, and write scientific articles and a final thesis. For more details please check the Graduate Schools Admission Requirements. 

Please note:

• You can apply online. We will not process applications sent by email and/or post. 
• As part of knowledge security, TU Delft conducts a risk assessment during the recruitment of personnel. We do this, among other things, to prevent the unwanted transfer of sensitive knowledge and technology. The assessment is based on information provided by the candidates themselves, such as their motivation letter and CV, and takes place at the final stages of the selection process. When the outcome of the assessment is negative, the candidate will be informed. The processing of personal data in the context of the risk assessment is carried out on the legal basis of the GDPR: performing a public task in the public interest. You can find more information about this assessment on our website about knowledge security.
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